General Structure Information
| PDB ID | 3f6k |
| HGNC Gene Label(s) | SORT1 |
| Structure Name | crystal structure of the vps10p domain of human sortilin/nts3 in complex with neurotensin |
| Resolution | 2.0Å |
| Reference | AUTH E.M.QUISTGAARD,P.MADSEN,M.K.GROFTEHAUGE,P.NISSEN,AUTH 2 C.M.PETERSEN,S.S.THIRUPTITL LIGANDS BIND TO SORTILIN IN THE TUNNEL OF A TEN-BLADEDTITL 2 BETA-PROPELLER DOMAIN.REF NAT.STRUCT.MOL.BIOL. V. 16 96 2009REFN ISSN 1545-9993PMID 19122660DOI 10.1038/NSMB.1543 |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 657 |
| Number Of SNVs | 147 |
| Number Of Permutations | 70937 |
| Optimal Distance Threshold | 29.0 |
| K Statistic | 0.366 |
| p-value | 0.061 |
COSMIC
| Number Of Residues | 657 |
| Number Of SNVs | 7 |
| Number Of Permutations | 3312 |
| Optimal Distance Threshold | 21.0 |
| K Statistic | 0.238 |
| p-value | 0.71 |
Ripley’s K Analysis Plots
ExACCOSMIC
Variant Set Comparisons
Cosmic vs. ExAC
| Number Of ExAC SNVs | 147 |
| Number Of COSMIC SNVs | 7 |
| Optimal Distance Threshold | 41.0 |
| K Statistic | 0.179 |
| p-value | 0.85 |
Pathogenic Proximity Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:109910100 | rs61797119 | I>V | A:91 | (39.98, 69.06, 13.13) |
| 1:109910084 | T>I | A:96 | (44.59, 73.82, 28.98) | |
| 1:109910033 | rs529693600 | R>Q | A:113 | (44.50, 73.29, 10.88) |
| 1:109898088 | rs567411233 | E>D | A:115 | (43.84, 70.72, 6.10) |
| 1:109898077 | K>R | A:119 | (44.01, 61.55, 7.85) | |
| 1:109898054 | rs181407789 | L>F | A:127 | (49.37, 81.18, 14.67) |
| 1:109898032 | R>Q | A:134 | (40.28, 82.10, 29.71) | |
| 1:109898018 | M>V | A:139 | (37.01, 76.59, 20.30) | |
| 1:109898014 | A>G | A:140 | (33.92, 80.24, 18.80) | |
| 1:109898012 | I>V | A:141 | (33.00, 77.72, 15.89) | |
| 1:109898003 | E>K | A:144 | (26.50, 77.30, 8.29) | |
| 1:109897150 | V>M | A:150 | (36.94, 83.32, 18.44) | |
| 1:109897147 | rs201636476 | L>V | A:151 | (40.56, 81.60, 20.36) |
| 1:109897141 | A>T | A:153 | (42.75, 85.14, 26.25) | |
| 1:109897119 | rs140106626 | R>H | A:160 | (42.73, 99.11, 30.27) |
| 1:109897120 | R>S | A:160 | (42.73, 99.11, 30.27) | |
| 1:109897107 | I>T | A:164 | (40.37, 87.93, 20.77) | |
| 1:109897086 | A>V | A:171 | (42.24, 78.38, 11.37) | |
| 1:109897082 | K>N | A:172 | (45.63, 78.48, 7.51) | |
| 1:109897069 | T>A | A:177 | (42.06, 91.65, 18.88) | |
| 1:109897066 | D>N | A:178 | (43.57, 93.96, 22.32) | |
| 1:109897044 | T>N | A:185 | (30.37, 85.26, 28.08) | |
| 1:109897045 | T>A | A:185 | (30.37, 85.26, 28.08) | |
| 1:109897041 | Q>P | A:186 | (31.17, 81.68, 24.20) | |
| 1:109897034 | COSM1497376 | M>I | A:188 | (27.06, 85.05, 21.45) |
| 1:109897022 | rs149456022 | Q>H | A:192 | (20.86, 86.98, 9.52) |
| 1:109896989 | E>D | A:203 | (32.06, 95.56, 34.26) | |
| 1:109893620 | G>V | A:205 | (28.14, 94.44, 29.71) | |
| 1:109893612 | rs147367732 | V>L | A:208 | (27.89, 94.65, 19.89) |
| 1:109893604 | K>N | A:210 | (28.73, 96.07, 13.59) | |
| 1:109890152 | rs572266365 | G>E | A:229 | (17.54, 86.13, 17.19) |
| 1:109890149 | S>L | A:230 | (15.66, 86.34, 14.24) | |
| 1:109890144 | N>H | A:232 | (20.38, 90.60, 13.20) | |
| 1:109890138 | I>V | A:234 | (19.68, 91.56, 20.68) | |
| 1:109890130 | F>L | A:236 | (18.79, 92.87, 26.64) | |
| 1:109890129 | T>S | A:237 | (17.92, 90.52, 30.97) | |
| 1:109890122 | Y>C | A:239 | (21.41, 94.45, 37.00) | |
| 1:109890116 | N>S | A:241 | (18.06, 97.22, 42.56) | |
| 1:109890117 | N>D | A:241 | (18.06, 97.22, 42.56) | |
| 1:109890107 | C>S | A:244 | (21.79, 89.54, 38.53) | |
| 1:109890105 | K>E | A:245 | (22.55, 87.22, 42.66) | |
| 1:109888483 | E>K | A:252 | (14.18, 95.19, 32.74) | |
| 1:109888478 | L>F | A:253 | (12.92, 91.43, 28.45) | |
| 1:109888473 | R>K | A:255 | (12.78, 94.22, 20.94) | |
| 1:109888459 | G>R | A:260 | (21.36, 99.64, 19.82) | |
| 1:109888444 | T>P | A:265 | (10.63, 97.55, 27.29) | |
| 1:109888432 | rs141749679 | K>E | A:269 | (8.34, 91.94, 37.63) |
| 1:109888414 | COSM3704809 | L>V | A:275 | (14.53, 81.55, 22.41) |
| 1:109888407 | G>E | A:277 | (11.29, 78.32, 17.74) | |
| 1:109888404 | rs552332611 COSM1332443 |
R>H | A:278 | (6.72, 79.71, 15.98) |
| 1:109888399 | rs377653401 | L>V | A:280 | (9.84, 84.62, 23.38) |
| 1:109884766 | R>S | A:293 | (2.25, 81.94, 35.72) | |
| 1:109884765 | rs141307400 | I>F | A:294 | (5.49, 80.54, 31.27) |
| 1:109884759 | V>I | A:296 | (4.21, 82.94, 25.14) | |
| 1:109884747 | rs371918164 | Q>E | A:300 | (10.22, 89.63, 18.28) |
| 1:109884707 | G>E | A:313 | (8.34, 78.00, 42.69) | |
| 1:109884692 | Y>C | A:318 | (8.85, 76.33, 34.28) | |
| 1:109884674 | rs72646565 | N>S | A:324 | (9.41, 72.48, 16.52) |
| 1:109884672 | rs78583579 | D>Y | A:325 | (8.67, 75.33, 13.43) |
| 1:109884654 | rs142613867 | H>Y | A:331 | (9.86, 69.36, 33.08) |
| 1:109884651 | rs369292571 | V>I | A:332 | (6.73, 71.33, 35.16) |
| 1:109883471 | D>G | A:347 | (-0.72, 74.68, 20.92) | |
| 1:109883468 | rs144932909 | D>G | A:348 | (0.04, 76.01, 16.96) |
| 1:109883465 | rs368245847 | R>Q | A:349 | (-2.08, 78.87, 19.98) |
| 1:109883463 | G>S | A:350 | (2.15, 77.93, 22.96) | |
| 1:109883442 | L>V | A:357 | (4.90, 61.78, 30.77) | |
| 1:109883435 | rs551934919 | R>Q | A:359 | (6.33, 59.79, 38.68) |
| 1:109883432 | H>R | A:360 | (10.17, 63.35, 33.10) | |
| 1:109883430 | L>V | A:361 | (13.89, 61.53, 35.51) | |
| 1:109883424 | T>A | A:363 | (17.76, 65.80, 38.39) | |
| 1:109883412 | rs375214942 | G>R | A:367 | (20.03, 68.37, 35.51) |
| 1:109883405 | rs202245759 | T>M | A:369 | (16.96, 64.39, 31.45) |
| 1:109883399 | F>Y | A:371 | (13.41, 64.18, 26.26) | |
| 1:109883396 | T>S | A:372 | (15.95, 61.45, 23.68) | |
| 1:109883391 | rs200994282 | V>M | A:374 | (14.53, 59.46, 17.96) |
| 1:109883382 | rs564227982 | L>F | A:377 | (11.34, 58.13, 13.06) |
| 1:109883378 | rs565948404 | R>H | A:378 | (7.25, 61.60, 11.63) |
| 1:109883373 | rs201821374 | V>I | A:380 | (10.20, 59.08, 17.98) |
| 1:109883367 | rs572350298 | I>V | A:382 | (13.07, 57.87, 24.29) |
| 1:109883357 | rs149508121 | V>A | A:385 | (9.55, 57.24, 34.12) |
| 1:109883358 | V>M | A:385 | (9.55, 57.24, 34.12) | |
| 1:109878962 | rs72646567 | S>F | A:391 | (11.69, 52.20, 39.69) |
| 1:109878960 | I>V | A:392 | (14.11, 54.22, 36.62) | |
| 1:109878956 | Q>R | A:393 | (10.52, 52.49, 34.32) | |
| 1:109878950 | rs529921012 | M>T | A:395 | (8.60, 55.14, 28.47) |
| 1:109878926 | R>K | A:403 | (0.46, 55.55, 23.76) | |
| 1:109878920 | rs144973301 | T>M | A:405 | (4.98, 52.60, 25.44) |
| 1:109878917 | H>R | A:406 | (6.71, 50.16, 28.59) | |
| 1:109878902 | E>G | A:411 | (12.11, 38.46, 20.20) | |
| 1:109878903 | rs72646568 | E>Q | A:411 | (12.11, 38.46, 20.20) |
| 1:109878893 | rs144141753 | E>G | A:414 | (17.95, 37.04, 28.31) |
| 1:109878873 | N>H | A:421 | (7.44, 37.65, 34.43) | |
| 1:109870193 | rs144898224 | I>V | A:435 | (26.21, 58.65, 32.41) |
| 1:109870184 | K>Q | A:438 | (29.42, 57.29, 37.96) | |
| 1:109870169 | M>V | A:443 | (28.18, 56.48, 24.29) | |
| 1:109870166 | A>T | A:444 | (24.36, 57.84, 24.77) | |
| 1:109870126 | A>G | A:457 | (21.77, 51.91, 22.97) | |
| 1:109869779 | S>N | A:460 | (18.30, 46.89, 30.34) | |
| 1:109869770 | D>V | A:463 | (10.55, 45.39, 34.91) | |
| 1:109869759 | V>L | A:467 | (23.21, 48.37, 38.20) | |
| 1:109869754 | M>I | A:468 | (23.99, 44.67, 35.57) | |
| 1:109869756 | COSM1747597 | M>L | A:468 | (23.99, 44.67, 35.57) |
| 1:109869738 | I>V | A:474 | (20.23, 48.11, 16.96) | |
| 1:109869717 | S>P | A:481 | (12.27, 46.70, 16.95) | |
| 1:109869711 | T>A | A:483 | (18.50, 43.50, 18.32) | |
| 1:109869695 | G>E | A:488 | (28.97, 45.13, 25.94) | |
| 1:109869686 | Y>C | A:491 | (33.12, 54.21, 23.48) | |
| 1:109869683 | Y>F | A:492 | (27.67, 53.92, 20.17) | |
| 1:109869660 | I>V | A:500 | (29.57, 52.35, 7.99) | |
| 1:109869656 | I>T | A:501 | (27.84, 50.93, 12.25) | |
| 1:109869646 | rs567941814 | I>M | A:504 | (35.61, 50.97, 20.15) |
| 1:109869640 | rs372322263 | H>Q | A:506 | (34.42, 50.56, 28.03) |
| 1:109869632 | rs200018778 | R>H | A:509 | (43.33, 45.23, 29.29) |
| 1:109869633 | R>C | A:509 | (43.33, 45.23, 29.29) | |
| 1:109869627 | rs144200520 | I>V | A:511 | (42.17, 49.03, 22.59) |
| 1:109867695 | G>S | A:521 | (24.51, 45.54, 12.93) | |
| 1:109867677 | Y>N | A:527 | (41.51, 47.13, 11.27) | |
| 1:109867673 | rs149226217 | T>M | A:528 | (43.99, 45.30, 14.11) |
| 1:109867664 | rs183424691 | R>K | A:531 | (50.73, 45.59, 18.09) |
| 1:109867658 | P>R | A:533 | (48.12, 48.87, 22.26) | |
| 1:109867635 | rs146248896 | S>A | A:541 | (33.09, 62.19, 13.50) |
| 1:109867613 | M>T | A:548 | (33.60, 57.11, 4.80) | |
| 1:109867595 | G>D | A:554 | (44.52, 58.21, 22.89) | |
| 1:109867590 | T>S | A:556 | (50.67, 55.27, 24.97) | |
| 1:109867578 | L>V | A:560 | (59.15, 55.00, 30.96) | |
| 1:109867554 | T>A | A:568 | (42.26, 58.50, 11.07) | |
| 1:109867550 | rs141785599 | I>T | A:569 | (40.15, 54.71, 9.86) |
| 1:109867545 | F>I | A:571 | (35.94, 52.81, 6.37) | |
| 1:109867539 | D>N | A:573 | (39.15, 51.35, -0.29) | |
| 1:109867534 | I>M | A:574 | (35.37, 49.00, 2.43) | |
| 1:109867535 | I>T | A:574 | (35.37, 49.00, 2.43) | |
| 1:109865735 | K>E | A:582 | (20.71, 48.85, -7.85) | |
| 1:109865726 | T>A | A:585 | (14.15, 49.23, -0.34) | |
| 1:109865711 | H>Y | A:590 | (5.65, 54.84, 12.23) | |
| 1:109865690 | Y>H | A:597 | (-7.39, 52.19, 5.14) | |
| 1:109865666 | Y>H | A:605 | (2.31, 62.58, 7.60) | |
| 1:109865660 | E>Q | A:607 | (6.74, 59.20, 5.87) | |
| 1:109865641 | R>H | A:613 | (18.31, 46.74, -0.78) | |
| 1:109865630 | rs72646577 | V>M | A:617 | (29.15, 46.97, 0.34) |
| 1:109865617 | G>D | A:621 | (27.11, 60.06, 0.18) | |
| 1:109865614 | rs376763956 | R>Q | A:622 | (29.84, 64.31, 1.99) |
| 1:109865615 | R>G | A:622 | (29.84, 64.31, 1.99) | |
| 1:109865611 | rs373818414 | D>G | A:623 | (25.59, 63.89, -2.26) |
| 1:109865573 | S>A | A:636 | (-9.72, 61.47, 13.07) | |
| 1:109860574 | R>H | A:648 | (-10.25, 63.07, 24.57) | |
| 1:109860572 | P>S | A:649 | (-13.44, 61.02, 28.62) | |
| 1:109860539 | E>Q | A:660 | (-16.10, 72.52, 37.70) | |
| 1:109860524 | rs546247342 | D>Y | A:665 | (-7.46, 75.19, 33.99) |
| 1:109860505 | Y>F | A:671 | (-4.87, 86.15, 34.65) | |
| 1:109860500 | R>G | A:673 | (-5.51, 87.31, 24.88) | |
| 1:109860497 | E>Q | A:674 | (-10.39, 86.88, 23.77) | |
| 1:109859575 | rs374583483 | R>Q | A:683 | (-6.31, 73.78, 17.88) |
| 1:109859543 | V>I | A:694 | (-13.65, 64.03, 10.93) | |
| 1:109859513 | K>E | A:704 | (-13.91, 84.48, 30.15) | |
| 1:109859485 | rs72646588 | S>N | A:713 | (-17.91, 92.16, 38.35) |
| 1:109859482 | rs146732214 | P>L | A:714 | (-15.60, 94.77, 38.54) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:109912176 | COSM1600498 | L>F | A:81 | (38.05, 68.31, 19.15) |
| 1:109897060 | COSM3470861 | P>S | A:180 | (37.26, 97.12, 25.20) |
| 1:109888414 | COSM3704809 | L>F | A:275 | (14.53, 81.55, 22.41) |
| 1:109884657 | COSM1600497 | M>V | A:330 | (7.51, 72.57, 28.88) |
| 1:109869756 | COSM1747597 | M>L | A:468 | (23.99, 44.67, 35.57) |
| 1:109869648 | COSM3355888 | I>V | A:504 | (35.61, 50.97, 20.15) |
| 1:109859567 | COSM3470854 | P>S | A:686 | (0.60, 70.10, 16.43) |